Previous studies have shown that metabolic acidosis is associated with enhanced Vmax of Na-H antiporter in brush border membranes of the rabbit kidney. We have recently shown that chronic hypercapnia and post-hypercapnia are also associated with enhanced Vmax of the Na-H antiporter. The mechanism responsible for this increase in Vmax of the Na-H antiporter is unknown. This proposal aims at elucidating the mechanisms responsible for alterations of the Na-H antiporter in acid-base disorders. We will address this issue by studying brush-border membranes from animals with acid-base disorders. To determine the mechanism whereby metabolic or respiratory acidosis increases the Vmax of the Na-H antiporter, we will measure binding of 3H amiloride analogs by brush border membranes. We will also study the Na-H antiporter in primary cultures of the proximal tubule of the rabbit. In this system it is possible to evaluate the role of intracellular pH, glucocorticoids, growth factors and protein synthesis in the adaptive increase in Vmax of the Na-H antiporter in acidosis. In addition, we will study the Na- H antiporter of brush-border membranes and the Na-HCO/3 cotransport in basolateral membranes of animals with acid-base disorders. We postulate that changes in Na-H antiporter are accompanied by parallel changes in NaHCO/3 cotransport. In addition, since glucocorticoids play a role in the adaptive increase in Vmax of Na-H antiporter in acidosis, we postulate that these hormones also influence the Na-HCO/3 cotransport. These studies will shed new light on the mechanisms responsible for the adaptation to acid-base disorders.